Hematoporphyrin derivative (HpD) has been shown to exhibit properties of preferential tumor localization, and of light activated tumor destruction via photosensitization. While the use of HpD phototherapy has been demonstrated to have great potential in the treatment of malignant disease, there still remains a significant lack of information pertaining to the areas of quantification of HpD uptake in malignant and normal tissue, as well as to cellular and tissue kinetics of HpD induced photoinactivation. The research described in this proposal is designed to utilize both in vivo and in vitro procedures to obtain information which can be used to enhance the efficacy and increase the applications of clinical HpD phototherapy. In vivo tissue distribution techniques will be employed to quantify HpD levels (using 3H-HpD) in both normal and malignant tissue of rabbits having transplanted ocular melanoma tumors. Quantitative studies will also be performed to determine the degree of enhanced differential tumor uptake of HpD which can be obtained by pretreatment of a tumor with x-rays. The addition of a radiation protecting agent (WR-2721) with HpD will be examined for its potential in selectively reducing normal tissue damage induced by HpD phototherapy. In vitro studies will be aimed at defining the action spectrum for HpD photoinactivation, determining what effect changes in dose rate have on the efficiency of HpD photoinactivation, performing split dose experiments to determine whether repair of sublethal damage can be observed following HpD phototherapy, and comparing the mutagenic potential of HpD phototherapy with that of ionizing radiation.